Article: Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells
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- Publisher Website: 10.1186/1471-2407-10-327
- Scopus: eid_2-s2.0-77954856721
- PMID: 20576118
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| Title | Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Friboulet, L2 Gourzones, C2 Tsao, SW1 Morel, Y4 Paturel, C4 Témam, S3 Uzan, C3 Busson, P2 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | BioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/ | ||||||
| Citation | Bmc Cancer, 2010, v. 10 [How to Cite?] DOI: http://dx.doi.org/10.1186/1471-2407-10-327 | ||||||
| Abstract | Background: There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.Methods: This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.Results: We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.Conclusions: Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas. © 2010 Friboulet et al; licensee BioMed Central Ltd. | ||||||
| ISSN | 1471-2407 2011 Impact Factor: 3.011 2011 SCImago Journal Rankings: 0.342 | ||||||
| DOI | http://dx.doi.org/10.1186/1471-2407-10-327 | ||||||
| ISI Accession Number ID | WOS:000280358000001
Funding Information: This study was supported by grants from the Ligue Nationale contre le Cancer (comites d'ile de France) and the Agence Nationale de la Recherche (EBV-inter). We thank Xiaodong Wang, Lin Li and Patrick Harran for generously providing RMT 5265 and HS 4404. | ||||||
| PubMed Central ID | PMC2928000 | ||||||
| References | References in Scopus |
| dc.contributor.author | Friboulet, L | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Gourzones, C | ||||||
| dc.contributor.author | Tsao, SW | ||||||
| dc.contributor.author | Morel, Y | ||||||
| dc.contributor.author | Paturel, C | ||||||
| dc.contributor.author | Témam, S | ||||||
| dc.contributor.author | Uzan, C | ||||||
| dc.contributor.author | Busson, P | ||||||
| dc.date.accessioned | 2010-10-31T10:37:26Z | ||||||
| dc.date.available | 2010-10-31T10:37:26Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Background: There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.Methods: This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.Results: We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.Conclusions: Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas. © 2010 Friboulet et al; licensee BioMed Central Ltd. | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Bmc Cancer, 2010, v. 10 [How to Cite?] DOI: http://dx.doi.org/10.1186/1471-2407-10-327 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1186/1471-2407-10-327 | ||||||
| dc.identifier.hkuros | 182820 | ||||||
| dc.identifier.isi | WOS:000280358000001
Funding Information: This study was supported by grants from the Ligue Nationale contre le Cancer (comites d'ile de France) and the Agence Nationale de la Recherche (EBV-inter). We thank Xiaodong Wang, Lin Li and Patrick Harran for generously providing RMT 5265 and HS 4404. | ||||||
| dc.identifier.issn | 1471-2407 2011 Impact Factor: 3.011 2011 SCImago Journal Rankings: 0.342 | ||||||
| dc.identifier.issue | 327 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmcid | PMC2928000 | ||||||
| dc.identifier.pmid | 20576118 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77954856721 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/124492 | ||||||
| dc.identifier.volume | 10 | ||||||
| dc.language | eng | ||||||
| dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/ | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | BMC Cancer | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | B M C Cancer. Copyright © BioMed Central Ltd. | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject.mesh | Adaptor Proteins, Vesicular Transport - metabolism | ||||||
| dc.subject.mesh | Antineoplastic Combined Chemotherapy Protocols - pharmacology | ||||||
| dc.subject.mesh | Apoptosis - drug effects | ||||||
| dc.subject.mesh | Inhibitor of Apoptosis Proteins - antagonists and inhibitors - genetics - metabolism | ||||||
| dc.subject.mesh | Neoplasms - genetics - metabolism - pathology | ||||||
| dc.title | Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Universite Paris-Sud XI
- Institut de Cancerologie Gustave Roussy
- Innate Pharma